title: Synthesis and the 5-HT6 receptor antagonistic effect of 3-arylsulfonylamino-5,6-dihydro-6-substituted pyrazolo[3,4]pyridinones for neuropathic pain treatment.
abstract: A novel series of 3-arylsulfonylamino-5,6-dihydro-6-substituted-1H-pyrazolo[3,4-c]pyridine-7-ones was designed and synthesized as 5-HT6 ligands. Among the derivatives synthesized, the lead compound, 12b, having piperidine functionality at the 6-position and (1-naphthyl)sulfonamino at the 3-position of the core structure showed the most potent 5-HT6 inhibitory activity in vitro, good stability without CYP liability, and good neuropathic pain alleviation activity in a rat animal model.
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institutes of Science and Technology (KIST), Seoul 136-791, Republic of Korea.
authors.forename: Vani Nelamane
authors.initials: VN
authors.lastname: Devegowda
authors.forename: Jin-Ri
authors.initials: JR
authors.lastname: Hong
authors.forename: Sungjin
authors.initials: S
authors.lastname: Cho
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Lim
authors.forename: Hyunah
authors.initials: H
authors.lastname: Choo
authors.forename: Gyochang
authors.initials: G
authors.lastname: Keum
authors.forename: Hyewon
authors.initials: H
authors.lastname: Rhim
authors.forename: Ghilsoo
authors.initials: G
authors.lastname: Nam
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009437:Neuralgia / Q000188:drug therapy; D011485:Protein Binding / Q000187:drug effects; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D011720:Pyrazoles; D011728:Pyridones; D011985:Receptors, Serotonin; C097216:serotonin 6 receptor
keywords: 5-HT(6) receptor antagonist; Arylsufonylamino-5,6-dihydro-pyrazolo[3,4-c]pyridine-7-one; Neuropathic pain; Synthesis